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Cancer News June 2014

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Cancer News June 2014 CANCER NEWS JUNE 2014 CANCER NEWS VOL MARCH 2007 NO. 1 RAJIV GANDHI CANCER INSTITUTE AND RESEARCH CENTRE 1 CANCER NEWS JUNE 2014 From the Desk of Director Research Therapeutic nuclear medicine is rapidly developing as an additional treatment modality. Oncology applications of nuclear medicine have entered into a new era as a result of greater understanding of the biological characteristics of tumors. In recent years, there has been greater emphasis on “targeted therapies”, designed to affect only the cancerous cells. There are currently hundreds of new pathway-targeted anticancer agents undergoing phase II and phase III clinical trials. Targeted radionuclide therapy is just one among the category of “targeted therapies.” At present, effective targeted radiopharmaceutical therapeutics have been developed and validated for a few tumor types, such as malignant lymphoma; and many other tumor types. The older nonspecific types of cancer treatments are still the dominant form of therapy. Radionuclide therapy is changing dynamically. Monoclonal antibody therapies for non-Hodgkins lymphoma using I-131; or imaging with Indium-111, followed by yttrium-90, are the next wave of a new generation of therapies. The basis of radionuclide therapy is simply the placement of the radionuclide in intimate contact with the target tissue. Particularly if short-range particle emitters are used, the absorbed dose to the target is very high as compared to non-target tissues. The route of administration may also pose different radiation safety issues. Oral or intravenous administration of radionuclides is very common, but other methods of administration also exist, such as insertion directly into a body cavity. Radionuclides are also gaining increasing importance by providing palliative and curative treatment in an increasing number of malignant diseases. Majority of radionuclides used in radionuclide therapy emit beta particles which have a low range of tissue penetration. A few emit auger electrons and alpha particles, and several others emit gamma rays and X-rays during their decay. The most successful radionuclide for thyroid therapy uses Iodine-131 as the nuclide for the treatment of benign hyperthyroid conditions, thyroid carcinoma, and peptidoreceptor radionuclide therapy (PRRT) for Neuroendocrine tumors. Both of which are successfully practiced. The present issue of Cancer News"Nuclear Medicine: Beyond Diagnostic" highlights the newer advances in the field of Radionuclide Therapy in cancer and features the regular articles, such as Special Feature, Guest Article, Perspective, In Focus, Research and Development, New Technologies, Globe Scan, In Focus and Clinical Trial. We are grateful for the contributions made by Dr V Rangarajan, Prof & Head, Dept Nuclear Medicine, Tata Memorial Hospital, Mumbai; Dr Sze Ting Lee, Dept of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Melbourne, Victoria, Australia; and Prof Cornelis A. Hoefnagel, Dean School of Theranostics WARMTH; Head, Dept of Nuclear Medicine [Retd], Netherlands Cancer Institute, Amsterdam, The Netherlands. Suggestions/ comments from the readers are welcome. Dr D C Doval CONTENTS • Special Feature: Overview of PET/CT in Radiotherapy Planning [3-7] • Guest Article: Targeted Metabolic Therapy of Neuroendocrine Tumors by I-131 MIBG [8-11] • Perspective: Systemic Radionuclide Therapy for Bone Pain Palliation in Cancer Patients [12-14] • Globe Scan: GMP Grade Rhenium-188-HEDP; Nuclear Medicine Therapy [14] • Research & Development: Radioiodine Therapy & Circulating Epithelial Cells; (153)Sm-EDTMP & Docetaxel in Prostate Cancer [15] • New Technologies: New Diagnostic and Therapeutic Techniques; Neuroendocrine Tumor Management [15] • In Focus: Alpha Radin (Ra223) Therapy: Opening A New Way to Treat Bone Metastasis in Prostate Cancer [16-17] • RGCON-2014: HIGHLIGHTS [18-19] Research & Analysis Team Published by: Rajiv Gandhi Cancer Institute & Research Centre Research Department Sector - 5, Rohini, Delhi - 110 085, India This publication aims at disseminating information on pertinent developments in its specific field of coverage. The information published does not, therefore, imply endorsement of any product/process/producer or technology by RGCI&RC. 2 CANCER NEWS JUNE 2014 SPECIAL FEATURE OVERVIEW OF PET/CT IN RADIOTHERAPY PLANNING Introduction Positron Emission Tomography (PET) is the use of radiopharmaceuticals labelled with positron emitters (radiation) to study physiologic processes in the body. This is opposed to CT which provides three-dimensional anatomical detail. The combination of PET and CT in an integrated scanner since the 1990’s has allowed the Fig 1: Example of 3D conformal radiotherapy. Higher fusion of physiological and anatomical information on the doses provided to the tumor (orange) than surrounding disease to be viewed in one image, and can, therefore, be tissues in the treatment field used in radiotherapy planning. The most useful utility CT or MRI, either in the same scanner system or with of PET has been improved staging, restaging and software registration, has allowed the integration of therapeutic monitoring of the disease. PET imaging with functional imaging obtained on PET with structural imaging various radiotracers takes advantage of the phenotypic provided by CT or MRI, to enable image-guided changes that occur in cancer cells to identify protein/ radiotherapy (IGRT). receptor expression and metabolic changes that are Radiotherapy planning has evolved over time, initially specific for tumors or are overexpressed compared to with the use of conventional x-ray which mimics optical normal tissue. and alignment properties of a linear accelerator, with Since the 1920s, cancer cells have been shown to contours done along the central axis of the beam and demonstrate an increased rate of glycolysis, requiring digitized into the treatment planning computer. This more glucose. Fluoro-2-deoxyglucose is molecularly includes standard external beam radiotherapy, conformal similar to glucose which is transported into cells via 3D-radiotherapy and intensity modulated radiotherapy GLUT1 receptors, where it is phosphorylated by (Fig 1). In conformal 3D-radiotherapy, there is no hexokinase but remains trapped within the cells as variation in intensity across each beam. More recently, fluoroglucose-6-phosphate which cannot enter the there has been an explosion in the use of “Intensity glycolytic pathway. When labeled with 18F, the molecule Modulated Radiotherapy” (IMRT), in which advanced is able to be detected by PET scanner which is increased 3D high precision radiotherapy is provided using in tumor cells due to increased GLUT1 receptors in computer controlled linear accelerators to deliver precise tumour cells. 18F-FDG PET has been shown to be the doses to specific areas within a tumor. The dose conforms most accurate non-invasive method to detect and stage more precisely to a 3D shape of the tumor by controlling many types of cancers. This has resulted in the improvement the intensity of the radiation mean in multiple small of patient management, avoiding unnecessary treatments volumes, and allows the concentration of certain doses and associated morbidity and costs. within certain areas of the tumor, whilst minimising the Radiotherapy is the use of ionizing radiation to treat dose to the surrounding normal tissue. The ratio of cancer by targeting cancer cells in a particular radiation normal to tumor tissue dose is reduced, resulting in a field. Although this inevitably includes normal cells higher and more effective radiation dose to tumor, with surrounding the cancer cells, the normal cells can recover fewer side effects. IMRT is most extensively used to from the radiation, but not the cancer cells. Radiotherapy treat prostate, head & neck and CNS malignancies, with is usually given with curative or palliative intent, and the increasing use in other solid tumors. dose given does depend on tumor type and the PET in Radiotherapy Planning surrounding tissues/organs. The advancement of The use of FDG PET imaging has had a significant technology to incorporate both structural imaging with impact on approximately 30-50% of disease 3 CANCER NEWS JUNE 2014 Table 1: Non-FDG PET Radiopharmaceuticals Used in Oncology Radiopharmaceutical Tumour Biology Clinical Applications 18F - F D G G luc o se M e ta b o lis m A ll tum o urs 11C -methionine Brain tumour 11C-choline Prostate cancer Proteins/amino acids 18F-DOPA Carcinoid tumour 18F-methyltyrosine (M ET) Musculoskeletal tumour 18F-thymidine (FLT) DNA Proliferation Treatment response (all) 18F-annexin V Apoptosis Treatment response (all) 18F-misonidazole (FMISO) Hypoxia Radiation planning (all) 18F-estradiol Receptor binding Breast cancer 18F-acetate Membrane/lipid synthesis Hepatocellular carcinoma management1, particularly in the appropriateness and treatment planning has been shown to improve the accuracy type of surgery, chemotherapy or radiotherapy in patients. of dose delivery and outcomes in treated patients. 18F-FDG PET/CT has been the modality with the most significant PET has been shown to improve target volume, and assist effect on radiotherapy planning recently, with an estimated in avoidance of relapse due to undiagnosed nodal or 55-60% of patients who have functional imaging, have distant metastases, in a range of tumours including lung potential changes in the target volumes and/or dose cancer and head and neck cancer (Fig 2) 2-4. distribution parameters. Whilst this most commonly refers In addition, the
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